United States Pharmacopeia (USP), one of the leading international agencies for setting standards for quality and safety of pharmaceuticals and food supplements, has been in the forefront for supporting research and development and has devised systematic standard procedures to ensure safety and quality of pharma and food ingredients that are being increasingly accepted across the globe. Apart from setting standards and supporting the growth of pharma and biotechnology industry, USP has also played a vital role in conducting training and organizing workshops for upgrading knowledge and skills of pharma professionals. In an email interview, Dr. Vijayaraghavan Srinivasan, Executive Vice President, Global science, USP, shares his views on the latest developments at USP with A Raju.
Could you throw light on some of USP’s latest R&D standards, particularly for vaccines and APIs being developed or in the process of development?
USP publishes quality standards for medicines and their ingredients in its compendia, United States Pharmacopeia and the National Formulary (USP–NF). These standards are used to test the identity, strength, quality and purity of medicines and their ingredients. USP-NF includes monographs, general chapters and allied reference materials for chemical and biological medicines, which include standards for vaccines and APIs.
Under the U.S. law, USP’s quality standards are applicable to drug substances and products legally marketed in the U.S. While USP develops drug quality standards, enforcement of those standards is the responsibility of the U.S. Food and Drug Administration (U.S. FDA). The US FDA’s purview also includes the safety and efficacy of drug substances and products. USP’s standards are also adopted and adapted—in part or in full—by other many other nations throughout the world, in support of their specific regulatory systems.
In addition, USP has been developing global public standards through the Medicines Compendium (MC)—a free, online resource providing public standards of medicines approved in any country. These include public standards for drug substances and excipients. Since the initiation of the MC in July 2011, much of the MC’s standards-development work has taken place at USP’s India site. To date, USP has developed authorized standards for approximately 70 drugs substances and drug products, most of which are chemical (small molecule) drugs and also includes three biological medicines. In the area of biologics, the focus of MC’s activities in India has been on vaccines and therapeutic proteins (primarily monoclonal antibodies). USP’s substantial progress in the area of vaccines has included the establishment of authorized standards for Hepatitis B antigen and Hepatitis B vaccine that are currently on the World Health Organization’s List of Essential Medicines.
Could you give a brief focus on USP’s current areas of R&D, upcoming investments, projects in pipeline and future plans relating to India?
USP-India is involved in the overall modernization of standards that appear in USP-NF as well as the development of global public standards for the Medicines Compendium. USP is expanding its success in working with Indian manufacturers, especially in the area of biologics. MC standards primarily are developed through Expert Committee volunteers. When USP initiated MC activities, the first MC Expert Committee was established in India and had a strong focus on chemical and biological medicines including vaccines and therapeutic proteins, as mentioned above. Since that time, the activities of the Expert Committee have grown, and a part of this committee now has expanded into a global Biologics Expert Committee, with scientists from South Korea, China, Brazil, Argentina and the U.S.—in addition to our members from India. Today, we have more than 145 staff in our USP-India site—all of whom are Indian nationals. We are excited about this continued growth. Further expansion of the USP India activities is under active consideration and discussion.
What are your views about the Indian pharmaceutical manufacturers in terms of quality standards and what are the areas you think they need to improve to reach world class standards?
Indian manufacturers continue to be significant players in the manufacture of global pharmaceutical products. It is important to note that a substantial percentage of all the Abbreviated New Drug Applications (ANDAs) approved by the U.S. FDA for the market entry into the US of generic pharmaceutical products are from Indian manufacturers.
It looks like USP has drawn some standards for prevention and control of microbiological contamination for pharmaceutical manufacturers. How significant are they for the industry?
The prevention and control of microbial contamination are critical for manufacturers of pharmaceuticals and health-related products. USP’s General Chapter <1116>, Microbiological Control and Monitoring of Aseptic Processing Environments provides guidance on the evaluation of clean rooms and ways to support microbiological control of aseptic environments.
Products manufactured in such environments include pharmaceutical sterile products, bulk sterile drug substances, sterile intermediates, excipients and, in certain cases, medical devices. Microbial content in non-sterile products is controlled to a level consistent with patient safety. Use of excessive controls that would add complexity and cost without a commensurate safety benefit is does not add value for either the patient or the manufacturer. Therefore, a pragmatic scientific approach to management of the microbial bioburden in non-sterile products requires consideration of patient risk and contamination control objectives to achieve a practical and appropriate level of risk management.
A new proposed General Chapter <1115> Bioburden Control of Non-sterile Drug Substances and Products outlines a risk-based approach to the control of potential contamination in non-sterile product manufacturing. A critical consideration in ensuring product quality is the prevention of conditions within the manufacturing facility or manufacturing process that would favour the proliferation of micro-organisms.
What are the major factors that may contribute to the microbiological contamination?
Raw material quality, water, manufacturing environments and personnel are some of the main factors that can contribute to potential contamination.
What are the important issues that need to be taken care of by a manufacturing company to avoid microbiological contamination?
Prevention of micro-organisms from entering open containers during processing, control of product bioburden and the bioburden of the manufacturing environment by reducing human-borne contamination risk are important factors governing the risk of microbial contamination in sterile products made by aseptic processing. Control of the microbiological quality of ingredients and water and the development of proper cleaning and sanitization procedures are the most critical factors in the prevention of microbiological contamination in non-sterile product manufacturing.
What is the significance of the upcoming prevention and control of microbiological contamination workshop which is being organized by USP and how relevant is it for the Indian pharmaceutical manufactures?
The workshop addresses USP standards related to prevention and control of microbial contamination. Adherence to such standards is vital for ensuring good and consistent product quality. USP’s standards apply to manufacturers throughout the world whose drug products, drug substances and excipients are manufactured or marketed in the U.S.
Apart from prevention and control of microbiological contamination, what are the other areas of focus at the workshop?
USP standards related to sterility testing and sterilization, and endotoxins will be addressed. Also, discussions will take place on sterility testing using modern, more rapid approaches.
Who can benefit from the workshop?
The workshop is relevant to the following stakeholders involved in pharmaceutical manufacturing such as:
- Microbiology laboratory supervisors and microbiologists
- Contract microbiology laboratory staff responsible for testing pharmaceuticals, biologics, dietary supplements, food ingredients, and medical device products
- Regulatory QA, QC and compliance personnel.